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"Susceptible strains of rodents fed high-fat diets overeat, gain fat and become profoundly insulin resistant. Dr. Jianping Ye's group recently published a paper showing that the harmful metabolic effects of a high-fat diet (lard and soybean oil) on mice can be prevented, and even reversed, using a short-chain saturated fatty acid called butyric acid (hereafter, butyrate).

The butyrate-fed mice remained lean and avoided metabolic problems. Butyrate increased their energy expenditure by increasing body heat production and modestly increasing physical activity. It also massively increased the function of their mitochondria, the tiny power plants of the cell."

Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats.
Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A.
Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E62-71.
PMID: 11404223

These data demonstrate that feeding cod protein prevents obesity-induced muscle insulin resistance in high fat-fed obese rats at least in part through a direct action of amino acids on insulin-stimulated glucose uptake in skeletal muscle cells.

"In an article published in the December 29, 2005, issue of the journal
Cell, the researchers report that knocking out a single gene encoding
the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin
production. Importantly, the scientists showed that a high-fat diet
suppresses the activity of GnT-4a and leads to type 2 diabetes due to
failure of the pancreatic beta cells.

"We have discovered a mechanistic explanation for beta cell failure
in response to a high-fat diet and obesity, a molecular trigger which
begins the chain of events leading from hyperglycemia to insulin
resistance and type 2 diabetes," said Jamey Marth, a Howard Hughes
Medical Institute investigator at the University of California, San
Diego (UCSD). Marth and first author Kazuaki Ohtsubo at UCSD
collaborated on the studies with researchers from the Kirin Brewery Co.
Ltd., and the University of Fukui, both in Japan."

Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes.
Ohtsubo K, Takamatsu S, Minowa MT, Yoshida A, Takeuchi M, Marth JD.
Cell. 2005 Dec 29;123(7):1307-21.
PMID: 16377570

The carnivore connection: dietary carbohydrate in the evolution of NIDDM.
Miller JC, Colagiuri S.
Diabetologia. 1994 Dec;37(12):1280-6.
PMID: 7895958

Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.
Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC Jr, Sebastian A.
Eur J Clin Nutr. 2009 Aug;63(8):947-55. Epub 2009 Feb 11.
PMID: 19209185
doi:10.1038/ejcn.2009.4

Conclusions: Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

DURHAM, N.C. -- Restricting carbohydrates, regardless of weight loss, appears to slow the growth of prostate tumors, according to an animal study being published this week by researchers in the Duke Prostate Center.

"Previous work here and elsewhere has shown that a diet light in carbohydrates could slow tumor growth, but the animals in those studies also lost weight, and because we know that weight loss can restrict the amount of energy feeding tumors, we weren't able to tell just how big an impact the pure carbohydrate restriction was having, until now," said Stephen Freedland, M.D., a urologist in the Duke Prostate Center and lead investigator on this study.

The researchers believe that insulin and insulin-like growth factor contribute to the growth and proliferation of prostate cancer, and that a diet devoid of carbohydrates lowers serum insulin levels in the bodies of the mice, thereby slowing tumor growth, Freedland said.

A Role of DNA-PK for the Metabolic Gene Regulation in Response to Insulin
Roger H.F. Wong, Inhwan Chang, Carolyn S.S. Hudak, Suzanne Hyun, Hiu-Yee Kwan, Hei Sook Sul
Cell 20 March, 2009 Volume 136, Issue 6, p1056
doi:10.1016/j.cell.2008.12.040    

Researchers at the University of California, Berkeley, have identified a gene that plays a critical regulatory role in the process of converting dietary carbohydrates to fat. In a new study, they disabled this gene in mice, which consequently had lower levels of body fat than their normal counterparts, despite being fed the equivalent of an all-you-can-eat pasta buffet.

The authors of the study, to be published in the March 20 issue of the journal Cell, say the gene, called DNA-PK, could potentially play a role in the prevention of obesity related to the over-consumption of high-carbohydrate foods, such as pasta, rice, soda and sugary snacks..

Westman EC, Feinman RD, Mavropoulos JC, Vernon MC, Volek JS, Wortman JA, Yancy WS, Phinney SD. Low-carbohydrate nutrition and metabolism.

The 'carnivore connection'--evolutionary aspects of insulin resistance.
Colagiuri S, Brand Miller J.
Eur J Clin Nutr. 2002 Mar;56 Suppl 1:S30-5. Review.
PMID: 11965520